Hepatitis A virus (HAV) is a picornavirus that causes acute liver disease in humans and some lower primates. As with other viruses of the picornavirus family, the genome of HAV contains three regions that encode the proteins of the virus. The structural proteins which form the viral capsid are encoded by the P1 region and the nonstructural proteins, which include viral proteinases, polymerase and other replication proteins are encoded by the P2 and P3 regions.
During a natural infection, the immune system of the infected individual produces antibodies to both the structural and nonstructural proteins (Stapleton et al (1995), J. Infect. Dis., 171 (Suppl. 1): S9-14). By comparison, an inactivated vaccine will induce antibodies to only the structural proteins and not to the nonstructural proteins (Robertson et al. (1993) J. Med. Virol., 40:76-82).
Currently marketed diagnostic assays used to determine HAV exposure detect antibodies to only the structural proteins. Thus, the current testing procedures cannot distinguish an individual with a natural infection from one who has been vaccinated. For diagnostic, safety and epidemiological reasons it is therefore important to develop an immunoassay which is capable of distinguishing whether antibodies were induced by vaccination or by an HAV infection. Previous studies using immunoprecipitation showed the production of antibodies to the entire P2 or P3 regions but not to the 3C proteinase specifically (Jia et al. (1992), J. Infec Dis., 165:273-280; Robertson et al. (1993), J. Med. Virol., 40:76-82).